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Purity: ≥98%
HA130 (HA-130) is a novel, potent and selective inhibitor of autotaxin (ATX, IC50 = 28 nM) with anticancer activity. HA130 inhibits the enzymatic activity of ATX, and slows T cell migration across lymph node HEVs in vivo. Ex vivo, HA130 blunts the TEM-promoting activity of ATX, paralleling its in vivo effects. Autotaxin (ATX) is an ectoenzyme that catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a bioactive lipid and a close relative of sphingosine 1-phosphate.
| Targets |
HA130: Autotaxin (ATX, phosphoric diester hydrolase) [1]
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| ln Vitro |
The capacity of ATX to stimulate TEM (transendothelial migration) is totally inhibited by HA130. At 0.3 μM, HA130 totally eliminated ATX's activity on TK1 tail-foot formation [1].
1. HA130 at a concentration of 0.3 μM blunts the polarization response of TK1 cells induced by ATX (5 μg/ml) plus LPC (1 μM), with a statistically significant difference (p < 0.001) compared to the ATX/LPC group, as assessed by CD44 accumulation in uropods [1] 2. Under physiologic shear conditions in a flow chamber, HA130 (0.3 μM) inhibits the transendothelial migration (TEM)-promoting activity of ATX/LPC on integrin-arrested T cells across a bEnd.3 endothelial monolayer, resulting in a significant reduction in the percentage of TEM T cells (p < 0.001 vs. ATX/LPC group) [1] |
| ln Vivo |
HEV migration of T cells across lymph nodes is slowed by HA130. Comparing animals treated with HA130 to those not, the "external HEV/internal HEV" ratio is lowered by 3–4 times [1]. When HA130 is injected subcutaneously, draining lymph nodes (LN) experience a notable increase in lymphocytes within the endothelial cell (EC) and sub-EC layers of HEV [2].
1. Administration of HA130 to mice impairs the entry of CFSE-labeled T cells into peripheral lymph nodes (PLN) and mesenteric lymph nodes (MLN). The ratio of CFSE-labeled T cells "outside high endothelial venules (HEVs)" to those "inside HEVs" in PLN and MLN of HA130-treated mice is significantly lower than that in DMSO control mice (p < 0.01) [1] 2. HA130 slows down the migration of T cells across lymph node HEVs in vivo, as demonstrated by immunofluorescence staining of HEVs (MECA 79) and CFSE-labeled T cells [1] |
| Cell Assay |
1. T cell polarization assay: TK1 lymphoma cells or naive mouse T cells were seeded on ICAM-1-coated substrata, and treated with ATX/LPC alone or in combination with HA130 (0.3 μM). After 7 minutes of incubation, the polarization of cells was determined by detecting the accumulation of CD44 (for TK1 cells) or CD43 (for naive T cells) in uropods. Each experiment was performed in triplicate wells, with results presented as means ± SDs, and the assay was repeated independently three times [1]
2. Transendothelial migration (TEM) assay: Mouse T cells were allowed to adhere to TNF-α-stimulated and CCL21-coated bEnd.3 endothelial cells under shear stress in a flow chamber. HA130 (0.3 μM) was added together with ATX/LPC, and the number of T cells undergoing TEM was counted over a 30-minute flow period, calculated as a percentage of adherent cells at 10 minutes. The assay was conducted in triplicate, with results shown as means ± SDs, and repeated three times independently [1] 3. T cell motility assay: Naive GFP+ CD4+ OTII T cells were seeded on crawling chambers coated with ICAM-1 and CCL21, and treated with ATX/LPC or ATX/LPC plus HA130. Cells were imaged every 15 seconds for 15 minutes, and cell tracks were analyzed by Imaris software to determine median velocity, turning angle, and total displacement. The experiment was repeated three times independently [1] |
| Animal Protocol |
1. Mice (C57BL/6 strain) were used for in vivo experiments. CFSE-labeled T cells were intravenously injected into mice, and HA130 (dissolved in DMSO) was administered to the treatment group, while the control group received an equal volume of DMSO [1]
2. Each group included 3 mice. For each mouse, 2 mesenteric lymph nodes (MLN) and 3 peripheral lymph nodes (PLN) were collected, and 6 non-consecutive sections were prepared for each lymph node. HEVs were stained with MECA 79, and CFSE-labeled T cells were visualized by fluorescence microscopy. The ratio of CFSE-positive cells outside HEVs to those inside HEVs was calculated, and the experiment was repeated three times [1] |
| References |
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| Additional Infomation |
1. HA130 is an inhibitor of autosecomotor (ATX) enzyme activity, which catalyzes the conversion of lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA) [1]. 2. By inhibiting ATX activity, HA130 interferes with the regulation of ATX/LPA axis-mediated navigation, motility, and transendothelial migration of naïve T cells, thereby blocking T cell homing to lymph nodes. This is complementary to the efflux function of sphingosine-1-phosphate in lymphocyte migration [1].
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| Molecular Formula |
C24H19BFNO5S
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|---|---|
| Molecular Weight |
463.2858
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| Exact Mass |
463.106
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| CAS # |
1229652-21-4
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| PubChem CID |
46911532
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
3.258
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
33
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| Complexity |
722
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| Defined Atom Stereocenter Count |
0
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| SMILES |
B(C1=CC(=CC=C1)COC2=CC=C(C=C2)/C=C\3/C(=O)N(C(=O)S3)CC4=CC=C(C=C4)F)(O)O
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| InChi Key |
VTNKMYWFWQTEHE-XKZIYDEJSA-N
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| InChi Code |
InChI=1S/C24H19BFNO5S/c26-20-8-4-17(5-9-20)14-27-23(28)22(33-24(27)29)13-16-6-10-21(11-7-16)32-15-18-2-1-3-19(12-18)25(30)31/h1-13,30-31H,14-15H2/b22-13-
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| Chemical Name |
(Z)-(3-((4-((3-(4-fluorobenzyl)-2,4-dioxothiazolidin-5-ylidene)methyl)phenoxy)methyl)phenyl)boronic acid
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| Synonyms |
HA-130; HA130; HA 130
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 39 mg/mL (~84.18 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.40 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.40 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1585 mL | 10.7924 mL | 21.5848 mL | |
| 5 mM | 0.4317 mL | 2.1585 mL | 4.3170 mL | |
| 10 mM | 0.2158 mL | 1.0792 mL | 2.1585 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 HA130 impedes T cell entry into lymph nodes.J Immunol.2012 Oct 15;189(8):3914-24. |
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 Binding of ATX to T cells.J Immunol.2012 Oct 15;189(8):3914-24. |
 ATX induces motility of na.J Immunol.2012 Oct 15;189(8):3914-24. |
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